Pregnancy and weight gain are accepted as going hand-in-hand but a group of New Zealand researchers has been collaborating to understand the mechanisms involved and to see if that can shed any light on what underlies obesity.
The HRC-funded programme is led by Professor Peter Shepherd from the Department of Molecular Medicine at The University of Auckland who has been working in close collaboration with Professor Dave Grattan from the University of Otago in Dunedin’s Department of Anatomy.
Professor Grattan says one of the significant concepts in the obesity field is that the body somehow becomes unresponsive to the normal feedback pathways that should limit eating.
“We have a hormone in our body called leptin which is produced by fat cells and should work to suppress appetite, and it is thought that in obesity this fails to occur properly.”
It was thought research into weight gain through the laying down of fat in pregnancy might provide valuable clues.
“It is an interesting model from our perspective in that it's probably the one time as an adult when it’s healthy to be gaining fat,” says Professor Grattan.
“The rationale behind it is that in pregnant women their appetite goes up, their food intake goes up, their body fat levels go up and their leptin levels go up - so theoretically the rising levels of leptin should suppress their appetite, but that doesn't happen. So pregnant women must become unresponsive to this hormone, a similar situation to that which occurs in obesity.”
Using animal models they found that females do become leptin resistant and they have identified the parts of the brain that no longer respond properly. They also identified the hormonal changes in the pregnancy that cause this change in appetite and are now trying to refine their understanding of how this occurs.
But what has also become clear is that the changes found in pregnancy are nothing like what happens in obesity.
“We’ve identified several mechanisms where the brain stops responding to leptin in pregnancy, that don't happen in various other models of obesity like diet-induced obesity, so it seems the changes in pregnancy are very specific responses being induced by the hormones of pregnancy,” says Professor Grattan.
The relationship between pregnancy and obesity is also looming larger because of the rising levels of obesity in the whole population, including pregnant women.
“Obesity has become the most common complication or cause of complication in pregnancy. It can affect the pregnancy and affect the mother’s health during pregnancy, leading to things like hypertension and gestational diabetes.
“It can also influence the developing offspring and it has been shown that offspring of mothers who are obese during pregnancy have a much greater predisposition to obesity when they grow up, so there is this generational loop that is also affected by food intake during pregnancy.
“So I think understanding how pregnancy hormones influence appetite and food intake will be important in helping us understand the challenges facing pregnant women.”
The research group has a number of projects that have spun-off from this, including collaborative research with a group in Germany which found that the hormone leptin is also required for normal responses to another hormone insulin in the brain.
Professor Grattan says that means that animals that become resistant to leptin, either in pregnancy or in obesity, also stop responding properly to insulin in the brain.
“We think this is going to be quite significant for understanding not only obesity but also how obesity can link to diabetes and I am really excited by the prospect that we might be understanding a mechanism where altered responses to leptin could lead to diabetes. The concept that obesity increases the risk of diabetes is very well accepted in obesity literature but the mechanism is not known and so we're starting to get some insights into that.
“That also feeds back into the pregnancy story again because one of the major risks of obesity during pregnancy is the development of gestational diabetes, so again we might be beginning to understand how that occurs.”
Professor Grattan says another exciting step forward in their HRC-funded research is the development of a new transgenic mouse model where they can block and manipulate the signalling of the key hormone prolactin, which they think is causing some of these changes during pregnancy.
“This really gives us the opportunity to prove some of what has previously been implied by our research.”
The next step will be to see if the changes they predict are occurring in pregnancy and lead to leptin resistance can also be shown in women.
Information: Professor David Grattan
University of Otago, Dunedin
Phone: (03) 479 7442
Information: Professor Peter Shepherd
The University of Auckland
Phone: (09) 373 7599 x 89891